Kidneys Inc.

medicine and nephrology updates and interesting cases by a practicing nephrologist in USA

Idiopathic membranous nephropathy, not idiopathic anymore

Idiopathic membranous nephropathy (IMN) was just that, idiopathic. No causative agent or etiology identified in patients. Like most other things in medicine, idiopathic only means, ‘not yet discovered’. A 2009 NEJM article changed the way we look at IMN and glomerulonephritis in general. Antibodies to M-type phospholipase (A2) receptor was found to be highly specific and sensitive in evaluation of patients with IMN. PLA2R is expressed in podocytes, and IgG4 antibodies co-localized in the glomerular deposits in patients with IMN. Anti-PLA2R Abs found positive in 70-80% of patients with IMN. Serum titers of anti-PLA2R antibodies also correlated with disease activity.  Recently in ‘correspondence’ in NEJM, there was an interesting perspective regarding the limitations of relying only on the circulating anti-PLA2R antibodies for detection.

Now there is more coming up as another genetic locus has been discovered for this unique disease. This in fact may fill the gap from the previous discoveries.

http://www.nejm.org/doi/full/10.1056/NEJMoa1009742

While the PLA2R has been located on 2q24, genome wide studies of single nucleotide polymorphism have shown HLA DQ1 (class2 alpha chain 1) as another focus on 6p21 (long arm of Chromosome 6).. This gene is associated with immune modulation and associated with type 1 diabetes, celiac disease and organ transplant rejection. In case of IMN, it seems to  facilitate the autoimmune response to PLA2R in the glomeruli. Homozygosity for both risk alleles gave an odds ratio of about 78.5. (CI 34.6- 178.2). However, this study included only French, Dutch and British groups, essentially, caucasian population. Looking forward to see more on this.

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